title: Attenuation of cerebral vasospasm and secondary injury by 17beta-estradiol following experimental subarachnoid hemorrhage.
abstract: OBJECTIVE
  Cerebral vasospasm remains a major complication in patients who have suffered a subarachnoid hemorrhage (SAH). Previous studies have shown that 17beta-estradiol (E2) attenuates experimental SAH-induced cerebral vasospasm. Moreover, E2 has been shown to reduce neuronal apoptosis and secondary injury following cerebral ischemia. Adenosine A1 receptor (AR-A1) expression is increased following ischemia and may represent an endogenous neuroprotective effect. This study was designed to evaluate the efficacy of E2 in preventing cerebral vasospasm and reducing secondary injury, as evidenced by DNA fragmentation and AR-A1 expression, following SAH.
  
  
  METHODS
  A double-hemorrhage model of SAH in rats was used, and the degree of vasospasm was determined by averaging the cross-sectional areas of the basilar artery 7 days after the first SAH. A cell death assay was used to detect apoptosis. Changes in the protein expression of AR-A1 in the cerebral cortex, hippocampus, and dentate gyrus were compared with levels in normal controls and E2-treated groups (subcutaneous E2, 0.3 mg/ml).
  
  
  RESULTS
  The administration of E2 prevented vasospasm (p < 0.05). Seven days after the first SAH, DNA fragmentation and protein levels of AR-A1 were significantly increased in the dentate gyrus. The E2 treatment decreased DNA fragmentation and prevented the increase in AR-A1 expression in the dentate gyrus. There were no significant changes in DNA fragmentation and the expression of AR-A1 after SAH in the cerebral cortex and hippocampus in the animals in the control and E2-treated groups.
  
  
  CONCLUSIONS
  The E2 was effective in attenuating SAH-induced cerebral vasospasm, decreasing apoptosis in the dentate gyrus, and reducing the expression of AR-A1 in the dentate gyrus after SAH. Interestingly, E2 appears to effectively prevent cerebral vasospasm subsequent to SAH as well as attenuate secondary injury by reducing both apoptosis and a compensatory increase in AR-A1 expression in the dentate gyrus.
authors.affiliation: Department of Neurosurgery, Graduate Institute of Medicine, College of Medicine, Taiwan.
authors.forename: Chih-Lung
authors.initials: CL
authors.lastname: Lin
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Dumont
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Su
authors.forename: Yee-Jean
authors.initials: YJ
authors.lastname: Tsai
authors.forename: Jih-Hui
authors.initials: JH
authors.lastname: Huang
authors.forename: Kao-Ping
authors.initials: KP
authors.lastname: Chang
authors.forename: Shen-Long
authors.initials: SL
authors.lastname: Howng
authors.forename: Aij-Lie
authors.initials: AL
authors.lastname: Kwan
authors.forename: Neal F
authors.initials: NF
authors.lastname: Kassell
authors.forename: Cheng-Hsing
authors.initials: CH
authors.lastname: Kao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy; D018891:Dentate Gyrus / Q000187:drug effects; D004958:Estradiol / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000032:analysis; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control
chemical_list: D043682:Receptor, Adenosine A1; D004958:Estradiol